What is the topic?
A protein in the brain called NR2A is part of a system that is important for learning and memory. Lupus patients can make antibodies to NR2A and some, but not all, studies have suggested that there might be a relationship between these antibodies and lupus brain inflammation (also known as neuropsychiatric lupus or NPSLE). There has been some evidence that if these antibodies are circulating in the bloodstream, then they may not be as much of a problem as if they cross over into the brain and spinal cord fluid.

What did the researchers hope to learn?
The researchers studied the relationship between anti-NR2A antibodies and different aspects of lupus, especially whether there might be a relationship between these antibodies and NPSLE in patients from Japan.

Who was studied?
181 people participated in the study, including 107 people with lupus, and 74 people with other inflammatory diseases (21 people with rheumatoid arthritis, 19 people with scleroderma, and 22 people with myositis), as well as 12 healthy people.

How was the study conducted?
All participants were recruited from the Institute of Rheumatology at Tokyo Women’s Medical University between 2000 and 2009. Only the lupus patients with anti-dsDNA antibodies were included in the study. Blood tests were done for several antibodies known to be found in lupus patients (anti-NR2A antibodies, as well as anti-dsDNA, anti-snRNP, anti-SM, and anti-SSA antibodies). Blood counts, and levels of inflammatory complement proteins, were also tested.

The different kinds of lupus in the patients were studied. Kidney biopsies were performed in 97 patients to investigate possible lupus nephritis. NPSLE was looked at by a physical exam, brain imaging (MRI), psychiatric interview, and special neuropsychological tests.

What did the researchers find?
The people with lupus had significantly higher levels of anti-NR2A antibodies than healthy people and patients with other inflammatory diseases.

All of the lupus patients studied had anti-dsDNA antibodies, 54% had anti-SSA antibodies, 36% had anti-snRNP antibodies, 25% had anti-NR2A antibodies, and 21% had anti-SM antibodies.

The average age of patients with NR2A antibodies was 34 and all were women. They had a range of types of lupus involvement: 63% had kidney involvement (nephritis), 48% had arthritis, and 48% had NPSLE. Only 22% of the overall lupus patients had NPSLE, so clearly more people with anti-NR2A antibodies had NPSLE than those without them.

What were the limitations of the study?
This was a “retrospective” study, meaning that the information about the patients being studied was recorded at some point in the past. When you don’t plan in advance what information to collect about patients the findings are not as accurate.

What do the results mean for you?
Anti-NR2A antibodies in the blood were associated with NPSLE in lupus patients from Japan. There are a number of studies that show differing results, but this might depend on the population being studied and the methods that are used to detect the antibodies, which are not standardized around the globe. More work will need to be done to figure out whether this antibody test might be useful in predicting NPSLE or as a target for new treatments.

The results of this study highlight the long-term effects of early NPSLE-related events on organ damage and recurrences of NPSLE-related events over time, in those having NPSLE-related events around the time of lupus diagnosis.